Preimplantation genetic diagnosis (PGD) is the screening of individual embryos for genetic disorders or gender determinination during the IVF process. At ART Reproductive Center, this procedure is a primary focus, and director Dr. David Hill is a nationally recognized expert in the use of PGD.

Here are some explanations and answers to common questions to help you learn more about this significant advance in reproductive technology:

• What is preimplantation genetic diagnosis (PGD)?
• Who can benefit from PGD?
• How is PGD performed?
• What can be determined about a pre-embryo by PGD testing?
• PGD-FISH (fluorescent in situ hybridization)
• PGD-PCR (polymerase chain reaction)
• PGD-CGH (Comparative Genomic Hybridization)
• Can PGD improve the chance of conceiving through IVF?
• What does the future hold for the genetic testing of embryos?

What is preimplantation genetic diagnosis (PGD)?

The preimplantation genetic diagnosis (PGD) procedure allows the screening of embryos for specific genetic traits before an embryo is implanted in a patient’s uterus. Also known as “embryo biopsy,” PGD allows couples at risk for certain genetic disorders to determine which of their embryos are affected, and which are not, before the embryos are used to establish a pregnancy.

We use PGD at the Southern California Reproductive Center to detect abnormalities in chromosomes, hereditary conditions, or gender determination.

Who can benefit from PGD?

PGD can increase the chance of pregnancy because it provides more intensive pre-screening of the embryos.  This also leads to a significant reduction in the chance of miscarriage. PGD can reduce the risk of multiple pregnancy because fewer embryos are needed for implantation. In addition, the patients who can benefit from PGD include:

• Couples who have a family history of inherited disease such as Tay Sacks or cystic fibrosis
• Couples who want to use gender determination to prevent a gender-linked disease
• Women with a history of unexplained miscarriage
• Women who have had repeated failures with IVF
• Women who are more than 39 years old

Family balancing is one of several issues that can arise with the concept of gender determination. Our SCRC physicians will be glad to discuss  the options available to couples that include determination of gender of their pre-embryos as part of the preimplantation genetic screening panel.

How is PGD performed?

PGD requires patients to undergo an in vitro fertilization (IVF) cycle in order to produce pre-embryos available for testing.

Before the transfer of a pre-embryo back to a woman’s uterus, one or two cells (called blastomeres) are removed from the available pre-embryos. These blastomeres are evaluated for normality. Following completion of the evaluation (typically one to two days), only the normal pre-embryos are transferred back to the woman’s uterus to establish a pregnancy.

What can be determined about a pre-embryo by PGD testing?

PGD can be used for determining chromosomal health (with PGD-FISH or PGD-CGH) or the presence or absence of specific genes related to hereditary disease (with PGD-PCR).

PGD-FISH (fluorescent in situ hybridization)

Chromosomal abnormalities occur when there is an incorrect number of chromosomes. Some chromosomes are more likely than others to become unpaired, which can lead to early embryonic demise (chromosomes 13, 16, 18, and 22) or affect term births, such as Down syndrome (trisomy 21). Numerical mistakes in the sex chromosomes can lead to Turner’s syndrome (XO), or Klinefelter’s syndrome (XXY). Sometimes, chromosomes can break apart and attach to other chromosomes, a condition known as translocation. Checking for normal chromosome pairing is done using a technique called fluorescent in situ hybridization (FISH), an established component of the preimplantation genetic diagnosis ( PGD) testing at our clinics.

PGD-CGH (comparative genomic hybridization)

PGD-CGH is a recent advance in the screening of pre-embryos for chromosomal normality. Its primary advantage is that CGH looks at all 23 pairs of chromosomes instead of a maximum of 12 pairs using PGD-FISH. PGD-CGH may require the cryopreservation of embryos while their cells are being tested; normal embryos are identified,thawed and transferred to the patient typically at her next ovulation cycle.

PGD-PCR (polymerase chain reaction)

The method of analysis for gene disorders is called polymerase chain reaction (PCR). PCR involves a technique that greatly multiplies the genetic code contained in a single blastomere, so that the specific gene or genes being looked for can be detected. Preimplantation genetic diagnosis is significantly enhanced by the use of PCR. Examples of hereditary conditions caused by gene disorders that PCR can help detect include:

• Cystic fibrosis
• Tay-Sachs disease
• Duchenne muscular dystrophy
• Sickle cell anemia
• X-chromosome-linked disorders
• Can PGD of pre-embryos improve the chance of conceiving through IVF?

Until the development of PGD, assisted reproductive technology labs could rely only on the appearance of pre-embryos to decide which ones were suitable for implantation into the patient’s uterus. The advent of PGD proved that normal-appearing pre-embryos frequently have an abnormal number of chromosomes, rendering them incompatible with the development of a normal pregnancy.

PGD allows embryologists to select pre-embryos that are balanced for the tested chromosomes. PGD testing enables the implantation of only selected pre-embryos, increasing the chance for pregnancy. In addition, because the quality of the pre-embryo has been proven, fewer pre-embryos are needed to establish a successful pregnancy, greatly diminishing the chances of a multiple pregnancy. Indeed, the use of PGD at the Southern California Reproductive Center has been instrumental in bringing many babies into the world.

What does the future hold for genetic testing of embryos?

In 1999, the genetic code of an entire human chromosome was sequenced (mapped). The completion of this revolutionary development in medical science allowed the continuing discovery of the sequence of the code that comprises specific units of genetic information. Genes are responsible for directing the construction of every cell in our body, down to the tiniest molecular detail. Therefore, it is reasonable to expect that the function of all genes, and the detection of abnormal genes, eventually will be categorized. This knowledge may in turn be used to reduce or eliminate susceptibility to hereditary, infectious, and cancerous diseases. Someday, only a single pre-embryo will be needed to establish a pregnancy — and it will be a healthy pregnancy.